Antiestrogens (Cancer treatment)
Antiestrogens are a class of drugs used primarily in the treatment of hormone-sensitive breast cancers. They work by interfering with estrogen receptors, effectively blocking estrogen from binding to cancer cells, which inhibits estrogen-stimulated growth of tumors. Notably, tamoxifen, toremifene, and fulvestrant are some of the key antiestrogens utilized in clinical practice. Tamoxifen, originally developed in the 1960s, has become a standard treatment option for both pre- and postmenopausal women, as well as men with breast cancer, and it is also employed to reduce cancer risk in susceptible individuals.
Antiestrogens are classified into two main subclasses: selective estrogen receptor modulators (SERMs) and estrogen receptor downregulators. SERMs can have both estrogenic and antiestrogenic effects depending on the specific cell type, while estrogen receptor downregulators completely degrade estrogen receptors, inhibiting their activity in all cell types. While effective, antiestrogens may cause side effects such as menopausal symptoms, gastrointestinal issues, and joint pain. It is also important to note that other hormone treatments, like aromatase inhibitors, work differently and are typically used in postmenopausal women. As treatment options continue to evolve, antiestrogens remain a critical component of hormone therapy for breast cancer.
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Antiestrogens (Cancer treatment)
ATC CODE: L02BA
DEFINITION: Antiestrogens interfere with the function of estrogen receptors. They are used in the treatment of hormone-sensitive breast cancers because of their ability to inhibit estrogen-stimulated cancer growth. These block hormones from attaching to cancer cells. In 2023, the Mayo Clinic listed three antiestrogens used in endocrine therapy for breast cancer: tamoxifen, toremifene, and fulvestrant.
Cancers treated:Breast cancer
Subclasses of this group: Selective estrogen receptor modulators (SERMs), estrogen receptor downregulators
Delivery routes: Administered either intramuscularly or orally in capsule, tablet, or solution form on an inpatient, outpatient, or at-home basis
How these drugs work: In 1962, ICI Pharmaceuticals synthesized the antiestrogen tamoxifen, what they hoped to be a new oral contraceptive. Although tamoxifen did not prove effective as a contraceptive, the discovery of hormone receptors in breast tissue by Elwood V. Jensen in 1966 led some researchers to believe that tamoxifen could be a therapeutic option in hormone-sensitive breast cancer. Clinical research in the early 1970s produced evidence that tamoxifen was effective in advanced breast cancers, and by the 1980s it became the treatment option of choice for hormone-sensitive breast cancers in pre- and postmenopausal women as well as men. Later it was approved for use in reducing the risk of breast cancer in patients who are susceptible to the disease.
Tamoxifen is a selective estrogen receptor modulator (SERM), a subclass of antiestrogens that act by binding to and changing estrogen receptors, resulting in both estrogenic and antiestrogenic effects depending on cell type. Antiestrogenic effects result in a slowing of cancer cell cycling and impaired deoxyribonucleic acid (DNA) replication. Estrogen receptor downregulators are used as a second-line treatment in hormone-sensitive breast cancer and act similarly to SERMs in that they antagonize the estrogen receptors of breast cells. These drugs, however, are pure estrogen receptor antagonists: independent of cell type, they completely degrade the estrogen receptor, resulting in a total loss of transcriptional activity in cancer cells.
Side effects: Common side effects of antiestrogens are menopausal symptoms (hot flashes, night sweats), vaginal discharge, vaginal irritation, vaginal bleeding, gastrointestinal (GI) symptoms (nausea and vomiting, constipation, diarrhea), fatigue, muscle cramps, joint pain, and thromboembolism. Although tamoxifen inhibits estrogen receptors in breast cells, it is a partial agonist in the endometrium and can cause endometrial changes, such as endometrial cancer, polyps, endometriosis, uterine fibroids, and ovarian cysts.
Other types of hormone treatments exist that work differently from antiestrogens. For example, aromatase inhibitors lessen the levels of hormones in the body. This method helps prevent cancer cells from acquiring the hormones needed to grow. Aromatase inhibitors are normally only administered to women who have already gone through menopause. Drugs of this type include Anastrozole (Arimidex), Exemestane (Aromasin), and Letrozole (Femara).
For females who have not experienced menopause, a different type of treatment prevents the ovaries from producing hormones. These treatments include medicines, surgery, and radiation. Often, targeted therapies are combined with hormone therapies.
Bibliography
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